Thyroid hormones are involved in the regulation of both development and metabolism. The major hormone-triiodothyronine (T3), binds a nuclear receptor (TR) which regulates the transcription of the gene products that mediate hormone response. Binding of T3 by TR induces a conformational change that alters the regulatory properties of the receptor. Our understanding of the mechanism by which hormone binding regulates receptor activity would be advanced by a structure of the TR ligand binding domain with T3 bound, at 2.0 E resolution. The domain consists largely of alpha helices, and reveals an unexpected binding mode for hormone, in which the hormone buried within the receptor as part of the hydrophobic core.